Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A retrospective analysis of 135 drug addicts followed between 1986 to 1987, was done, in order to asses the seroprevalence of hepatitis B virus (HBV), hepatitis Delta virus (HDV), hepatitis C virus (HCV) and Human Immunodeficiency virus (HIV), as also their clinical and prognostic significance. A high prevalence of HBV, HDV and HCV infection was observed in this study: 81%, 64% and 83% respectively; in contrast just one case was positive for HIV. Among the drug addicts the frequency of multiple infections (HBV/HCV 51.6%; HBV/HDV/HCV 18.7%; HBV/HDV 2.2%; HCV/HIV 1.1%) was highest in comparison with isolated (HBV 5.5%; HCV 12.1%) or absent infection (73.6% vs 17.6% vs 8.8% respectively; p less than 0.001). Eleven of 12 (92%) patients with Delta hepatitis and HCV superinfection were seronegative for IgM anti-HD; in contrast the case without HCV superinfection was IgM anti-HD positive. In the former group the Alanine Amino-transferases (ALT) were significantly lower comparatively with those HBV positive patients superinfected by HCV (97 +/- 92 IU/L vs 249 +/- 125 IU/L; p = 0.001), and were not different from drug addicts with isolated HCV infection (62 +/- 49 IU/L). The results of this study indicate, a low prevalence of HIV infection in the Portuguese drug addicts and a high frequency of multiple HBV, HDV and HCV infection in the same period of study. Our observations suggest that HCV may have the capacity to inhibit the replication and pathogenic activity of hepatitis Delta virus.
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PMID:[Viral infections in intravenous drug addicts. Clinical and prognostic significance]. 178 66

Using a second generation enzyme immunoassay (ELISA) for the detection of antibodies against Hepatitis C virus (HCV), we investigated the frequency of antibodies anti-HCV and the Alanine Aminotransferase (ALT) plasma levels of 200 patients without history of viral hepatitis, liver diseases, blood transfusions, intravenous drugs abuse, homosexuality, hemodialysis, infection by Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), nor workers of health services. There plasma samples (1.5%), were positives for antibodies anti-HCV, all of these samples were confirmed by RIBA (Recombinant Immunoblot Assay). In these three patients, the ALT plasma level were more than two folds the normal upper limit, another six patients had high ALT levels but less than one fold the normal upper limit. None of the infected patients had any clues that suggested the possible way of infection in the clinic history. We concluded that the incidence of Hepatitis C in the studied patients is 1.5% and that the ALT levels could be used to identify Hepatitis C infection.
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PMID:[Anti-HCV in patients without risk factors for hepatitis C. Prospective study in 200 patients]. 750 1

A series of amino acid substitutions were carried out in the V3 loop of SIV gp120 to investigate their effects on binding of the envelope to CD4 and neutralizing monoclonal antibodies. Alanine replacement of two adjacent arginines at the amino terminus of V3 resulted in a molecule that bound neither sCD4 nor conformation-dependent neutralizing monoclonal KK5 and KK9. A similar substitution of two amino acids, lysine and arginine, in the carboxyl half of V3 disrupted binding to KK9 without affecting CD4 binding. Removal of V3 from the envelope gave rise to a molecule that was not secreted. These data suggest a close linkage between V3 and CD4 binding domains of gp120, although neutralizing antibodies directed to V3 do not block binding of gp120 to CD4. We propose that differences in the modes of interactions of the V3 disulfide loops with CD4 in SIV and HIV may be responsible for the observed different neutralizing properties of the two V3 loops.
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PMID:Alanine substitution of two arginines in amino terminus of V3 of SIV disrupts CD4 binding whereas a similar replacement of two amino acids, lysine and arginine, in the carboxyl half of V3 prevents binding of a neutralizing monoclonal antibody. 855 7

Residues 259-284 of HIV-1 reverse transcriptase exhibit sequence homology with other nucleic acid polymerases and have been termed the "helix clamp" (Hermann, T., Meier, T., Gotte, M., and Heumann, H. (1994) Nucleic Acids Res. 22, 4625-4633), since crystallographic evidence indicates these residues are part of two alpha-helices (alpha H and alpha I) that interact with DNA. Alanine-scanning mutagenesis has previously demonstrated that several residues in alpha H make important interactions with nucleic acid and influence frameshift fidelity. To define the role of alpha I (residues 278-286) during catalytic cycling, we performed systematic site-directed mutagenesis from position 277 through position 287 by changing each residue, one by one, to alanine. Each mutant protein was expressed and, except for L283A and T286A, was soluble. The soluble mutant enzymes were purified and characterized. In contrast to alanine mutants of alpha H, alanine substitution in alpha I did not have a significant effect on template.primer (T.P) binding as revealed by a lack of an effect on Km, T.P, Ki for 3'-azido-2',3'-dideoxythymidine 5'-triphosphate, koff, T.P and processivity. Consistent with these observations, the fidelity of the mutant enzymes was not influenced. However, alanine mutagenesis of alpha I lowered the apparent activity of every mutant relative to wild-type enzyme. Titration of two mutants exhibiting the lowest activity with T.P (L282A and R284A) demonstrated that these mutant enzymes could bind T.P stoichiometrically and tightly. In contrast, active site concentrations determined from "burst" experiments suggest that the lower activity is due to a smaller populations of enzyme bound productively to T.P. The putative electrostatic interactions between the basic side chains of the helix clamp and the DNA backbone are either very weak or kinetically silent. In contrast, interactions between several residues of alpha H and the DNA minor groove, 3-5 nucleotides from the 3'-primer terminus, are suggested to be critical for DNA binding and fidelity.
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PMID:Role of the "helix clamp" in HIV-1 reverse transcriptase catalytic cycling as revealed by alanine-scanning mutagenesis. 864 17

Alanine scanning mutagenesis was undertaken to evaluate the structural significance of Met230-His235 of the 66 kDa subunit of p66/p51 human immunodeficiency virus reverse transcriptase (HIV-1 RT). Together with Glu224-Trp229, these residues provide the framework of the p66 "primer grip", whose proposed role is maintaining the primer terminus in an orientation appropriate for nucleophilic attack on an incoming dNTP. Of these residues, altering Leu234 results in a p66 subunit incapable of associating into heterodimer. The remaining selectively mutated enzymes were successfully reconstituted and purified to homogeneity for evaluation of RT-associated activities. We show here that alterations to any residue within the p66-Trp229-Met230-Gly231-Tyr232-quartet alter functions associated with both the DNA polymerase and ribonuclease H (RNase H) domains. Detailed analysis of mutant p66Y232A/p51 with an intact or a model "precleaved" RNA-DNA hybrid suggests an altered RNase H phenotype could result from relocation of template-primer in the nucleic acid binding cleft. As a consequence, template nucleotide-8 is positioned in the immediate vicinity of the RNase H catalytic center rather than nucleotide-17.
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PMID:Alterations to the primer grip of p66 HIV-1 reverse transcriptase and their consequences for template-primer utilization. 867 16

Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) oligomerization was investigated by coexpressing wild-type and truncated envelope glycoproteins to determine the minimum sequence required for mutant-wild-type hetero-oligomerization. The gp41 putative amphipathic alpha-helix, Leu-550 to Leu-582, was essential for hetero-oligomer formation. Alanine substitution of 9 of the 10 residues composing the gp41 amphipathic alpha-helix 4-3 hydrophobic repeat sequence was required to inhibit mutant-wild-type hetero-oligomerization and to render the envelope glycoprotein precursor, gp160, monomeric. This indicates that multiple hydrophobic contacts contribute to the stable envelope glycoprotein oligomeric structure. Single alanine substitutions within the hydrophobic repeat sequence did not affect gp160 oligomeric structure but abolished syncytium-forming function. Some mutations also diminished gp160 processing efficiency and the association between gp120 and gp41 in a position-dependent manner. These results indicate that the gp41 amphipathic alpha-helix 4-3 hydrophobic repeat sequence plays a central role in HIV-1 envelope glycoprotein oligomerization and fusion function.
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PMID:Human immunodeficiency virus type 1 envelope glycoprotein oligomerization requires the gp41 amphipathic alpha-helical/leucine zipper-like sequence. 903 36

One of the high risk groups of hepatitis C virus infection is intravenous drug abusers (IVDAs). The study of HCV seroprevalence and some qualitative risk factors in this target group can be valuable for prevention of the infection. During June to October 1992, a cross-sectional study of 150 intravenous male drug abusers seeking medical treatment at Phranangkhlao and Rajavithi Hospitals was conducted. Blood specimens were collected for determining anti-HCV antibody by EIA. An in-depth interview was carried out searching for some qualitative risk factors in anti-HCV positive and negative IVDAs. It was found that 95.33% of studied IVDAs were positive for anti-HCV antibody. There was no significant difference between the prevalence of anti-HCV and their ages (p > 0.05). The antibody prevalence trended to be higher with the longer duration of drug use. The positive rate of IVDAs who had injected more than 8 years was significantly higher than that of IVDAs who had injected less than 2 years (100% and 85.71), p = 0.004. Alanine amino-transferase (ALT) levels and anti-HIV antibodies were determined. IVDAs with higher levels of anti-HCV had higher percentages of ALT abnormality and anti-HIV positive rates. Data from in-depth interview showed that the longer duration of imprisonment, tattoo/ear piercing, extramarital relations without using condoms, the longer duration of drug use and needle/syringe sharing were potential risk factors for HCV infection in this target group.
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PMID:High hepatitis C seroprevalence in Thai intravenous drug abusers and qualitative risk analysis. 925 62

We have previously demonstrated that the Gag p9 protein of equine infectious anemia virus (EIAV) is functionally homologous with Rous sarcoma virus (RSV) p2b and human immunodeficiency virus type 1 (HIV-1) p6 in providing a critical late assembly function in RSV Gag-mediated budding from transfected COS-1 cells (L. J. Parent et al., J. Virol. 69:5455-5460, 1995). In light of the absence of amino acid sequence homology between EIAV p9 and the functional homologs of RSV and HIV-1, we have now designed an EIAV Gag-mediated budding assay to define the late assembly (L) domain peptide sequences contained in the EIAV p9 protein. The results of these particle budding assays revealed that expression of EIAV Gag polyprotein in COS-1 cells yielded extracellular Gag particles with a characteristic density of 1.18 g/ml, while expression of EIAV Gag polyprotein lacking p9 resulted in a severe reduction in the release of extracellular Gag particles. The defect in EIAV Gag polyprotein particle assembly could be corrected by substituting either the RSV p2b or HIV-1 p6 protein for EIAV p9. These observations demonstrated that the L domains of EIAV, HIV-1, and RSV were interchangeable in mediating assembly of EIAV Gag particles in the COS-1 cell budding assay. To localize the L domain of EIAV p9, we next assayed the effects of deletions and site-specific mutations in the p9 protein on its ability to mediate budding of EIAV Gag particles. Analyses of EIAV Gag constructs with progressive N-terminal or C-terminal deletions of the p9 protein identified a minimum sequence of 11 amino acids (Q20N21L22Y23P24D25L26S27E28I29K30) capable of providing the late assembly function. Alanine scanning studies of this L-domain sequence demonstrated that mutations of residues Y23, P24, and L26 abrogated the p9 late budding function; mutations of other residues in the p9 L domain did not substantially affect the level of EIAV Gag particle assembly. These data indicate that the L domain in EIAV p9 utilizes a YXXL motif which we hypothesize may interact with cellular proteins to facilitate virus particle budding from infected cells.
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PMID:Equine infectious anemia virus utilizes a YXXL motif within the late assembly domain of the Gag p9 protein. 926 74

We constructed a recombinant human immunodeficiency virus type 1 (HIV-1) provirus called R7-GFP that expresses a modified form of a green fluorescent protein (GFP) from the jellyfish Aequorea victoria by substituting GFP-coding sequences for Nef-coding sequences. Alanine was substituted for serine at amino acid position 65 in the modified GFP, resulting in markedly increased fluorescence at an excitation wavelength of 488 nm as compared to wild-type GFP. The replication kinetics of R7-GFP were identical to that measured with an isogenic, nef-negative strain lacking GFP. Expression of GFP by replication-competent HIV-1 allowed simultaneous quantitation of viral infection and cell surface CD4 levels, revealing rapid and nearly complete CD4 downregulation on R7-GFP-infected PBMCs.
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PMID:Use of a green fluorescent protein as a marker for human immunodeficiency virus type 1 infection. 928 11

TRBP is a cellular protein that binds to the HIV-1 leader RNA, TAR. Circular dichroism experiments have shown that a 24 amino acid peptide (TR1), located within a dsRNA binding domain (dsRBD) of TRBP, binds TAR with a 3:1 stoichiometry, eliciting a conformational change involving base unstacking. The binding characteristics of synthetic structural variants of TAR indicate that guanine residues play a key role in the TR1-RNA interaction and that binding sites exist in the upper-stem/loop and lower stem region of TAR. Deletion analysis of TR1 has led to the identification of a 15 amino acid subpeptide (TR13) which is necessary and sufficient to bind to the high affinity upper-stem/loop binding site of TAR. Alanine scanning of TR13 has revealed that mutations in either Lys or Arg residues result in altered TAR-binding, and molecular modelling/docking experiments have shown that the two Arg residues of TR13 can interact with two appropriately spaced guanine residues in the upper-stem/loop of TAR. The TR13 lysine residues appear to be essential for maintaining structural integrity and the correct positioning of the Arg side-chains. We propose that TRBP binds TAR by means of a "2-G hook" motif and that the binding specificity of this particular member of the family of double-stranded RNA-binding proteins lies within the highly conserved dsRBD core motif. Finally, our results also suggest that TRBP may function in vivo by modifying the tertiary structure of TAR RNA.
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PMID:An Arg/Lys-rich core peptide mimics TRBP binding to the HIV-1 TAR RNA upper-stem/loop. 964 86


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